DESCRIPTION (Scanned from the Applicant's Abstract): Type 1 diabetes is a polygenic, chronic metabolic disease characterized by the progressive ablation of insulin-producing beta cells by autoimmunity. Regular insulin injections do not maintain blood glucose near normal levels at all times and consequently patients develop serious secondary clinical complications. While pancreatic and islet transplantations consistently establish euglycemic states and significantly reduce long-term complications, availability of the grafts is severely limited. Thus, there is an urgency to develop a beta cell/islet replacement therapy for Type 1 diabetic patients. The mammalian hematopoietic stem cells (HSCs) produce at least 8 distinct lineages of mature blood cells while mesenchymal stem cells (MSCs) produce multiple lineages of mature cells. The wealth of information on the growth and differentiation of these stem cells is vast, and purified HSCs are routinely used in the clinical setting and both HSCs and MSCs are commercially available for research purposes. Thus, investigating the feasibility of differentiating human HSCs and MSCs into pancreatic pathway will be of immense importance in curing Type 1 diabetes, and in the realization of autologous stem cell-derived insulin producing cell/islets for implantation. In this SBIR Phase I proposal, we will specifically: (1) characterize human bone marrow derived CD34+ HSCs and CD34-MSCs for the expression of developmental genes involved in the generation of islets/pancreas following treatments with various factors in vitro; and (2) determine the functional capability of the differentiated cells in vitro. A successful completion of the Phase I study will lay the foundation for a more detailed Phase II grant proposal that will involve in vivo functional studies in diabetic animal models. PROPOSED COMMERCIAL APPLICATION: This research project has the potential to produce glucose-responsive insulin producing cells/islets for implantion into every single insulin?dependent Type 1 & 2 diabetics. All that would be required from the individuals is their peripheral blood, or bone marrow samples. Also, cells that are at different stages of differentiation can be used for drug discovery research related to mesenchymal and pancreatic systems.